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Immunomodulation of thalidomide is represented by the antiinflammatory effect through inhibition of tumor necrosis factor alpha and costimulatory effect on human CD8+ T cells. We investigated the efficacy and safety of a 24-wk course of thalidomide at a dosage of 200 mg/day in eight patients with HCV chronic hepatitis nonresponders to interferon alpha plus ribavirin. We observed a significant mean decrease of serum aminotransferases and gamma-glutamyltransferases of 39% and 61%, respectively (p = 0.017 and 0.02). Tumor necrosis factor-alpha in vitro production in mononuclear cells decreased with thalidomide in all the subjects (p = 0.028). Perforin- and granzyme-specific mRNA expression increased under thalidomide without statistical significance. A positive correlation between biochemical and immunological parameters was observed with higher increase of granzyme and perforin values in patients showing reduction of aminotransferases. Finally upregulation of T-helper 1 cytokine expression as mean interferon gamma/IL-10 ratio was evidenced. Thalidomide was well tolerated. In conclusion, thalidomide was able to reduce liver enzymes in six out of eight patients with chronic hepatitis C and to reduce tumor necrosis factor alpha production, representing a promising new approach for the treatment of HCV infection.

Objectives: A major side effect of antiretroviral drugs is nucleoside reverse transcriptase inhibitor (NRTI)-related mitochondrial toxicity, the in vivo diagnosis of which is difficult and not yet standardized. We used the [ 13 C]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infected patients receiving antiretroviral therapy. Patients and methods: The [ 13 C]methionine breath test was performed in healthy subjects (n = 10), HIV-infected patients on antiretroviral therapy with (n = 6) and without (n = 15) hyperlactataemia and naive HIV-infected patients (n = 11). After oral administration of [ 13 C]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath 13 CO 2 enrichment, expressed as δ over baseline (DOB) every 15 min for 120 min by mass spectrometry. Results: The four study groups showed a significant difference in 13 CO 2 exhalation (P = 0.001). HIV-infected patients on antiretroviral therapy with normal serum lactate had reduced exhalation of 13 CO 2 compared with healthy subjects (DOB mean peak: 8.82 ± 0.62 versus 11 ± 0.9, P